Idiopathic inflammatory myopathies (IIM) are a group of rare autoimmune disorders characterized by muscle inflammation and progressive weakness. The cause of IIM is unclear but it is believed that disease expression may be triggered by unknown factors in genetically predisposed individuals. Diagnosis is based on a combination of clinical, laboratory and electromyography findings. Muscle biopsy is the definitive diagnostic test. Research into IIM has been limited by the rarity of the disease, a somewhat insidious onset, difficulties with classification and diagnostic methods and heterogeneous study populations making cross-study evaluations difficult. This paper reviews the diagnostic and classification criteria of the IIM and examines epidemiological studies that have been performed, focusing on demographics.
"Noteworthy, muscle fibers do not physiologically express MHC-I molecules and are therefore intrinsically resistant to CD8+ T cells autoimmune aggression –. In human polymyositis, MHC-I is upregulated at the surface of myofibers and the presence of MHC-I-expressing myofibers surrounded by CD8+ lymphocytes is one of the hallmarks and diagnosis criteria of polymyositis –. Future experimental studies should address whether induction of stable MHC-I expression in muscle by gene transfer could lead to the breakage of tolerance in this model. "
[Show abstract][Hide abstract] ABSTRACT: Muscle potentially represents the most abundant source of autoantigens of the body and can be targeted by a variety of severe autoimmune diseases. Yet, the mechanisms of immunological tolerance toward muscle autoantigens remain mostly unknown. We investigated this issue in transgenic SM-Ova mice that express an ovalbumin (Ova) neo-autoantigen specifically in skeletal muscle. We previously reported that antigen specific CD4(+) T cell are immunologically ignorant to endogenous Ova in this model but can be stimulated upon immunization. In contrast, Ova-specific CD8(+) T cells were suspected to be either unresponsive to Ova challenge or functionally defective. We now extend our investigations on the mechanisms governing CD8(+) tolerance in SM-Ova mice. We show herein that Ova-specific CD8(+) T cells are not detected upon challenge with strongly immunogenic Ova vaccines even after depletion of regulatory T cells. Ova-specific CD8(+) T cells from OT-I mice adoptively transferred to SM-Ova mice started to proliferate in vivo, acquired CD69 and PD-1 but subsequently down-regulated Bcl-2 and disappeared from the periphery, suggesting a mechanism of peripheral deletion. Peripheral deletion of endogenous Ova-specific cells was formally demonstrated in chimeric SM-Ova mice engrafted with bone marrow cells containing T cell precursors from OT-I TCR-transgenic mice. Thus, the present findings demonstrate that immunological tolerance to muscle autoantigens involves peripheral deletion of autoreactive CD8(+) T cells.
PLoS ONE 05/2012; 7(5):e36444. DOI:10.1371/journal.pone.0036444 · 3.23 Impact Factor
"There is a slight female predominance (F:M ¼ 1.5:1.0) Furthermore, IBM is the most common subtype in men over the age of 50 [Cox et al. 2010]. Under age 50, DM is more common than PM [Dalakas and Hohlfeld, 2003]. "
[Show abstract][Hide abstract] ABSTRACT: The idiopathic inflammatory myopathies (IIMs) are rare disorders with the unifying feature of proximal muscle weakness. These diseases include polymyositis(PM), dermatomyositis (DM) and inclusion body myositis (IBM) as the most common. The diagnosis is based on the finding of weakness on exam, elevated muscles enzymes, characteristic histopathology of muscle biopsies, electromyography abnormalities and rash in DM. Myositis-specific antibodies have been helpful in defining subsets of patients with different responses to treatment and prognosis. The cornerstone of therapy is corticosteroids with the addition of other immunosuppressives in severe or refractory disease or patients with intolerable side effects. IBM is particularly difficult to treat but is more slowly progressive as compared with PM or DM. There is still a great need to find more effective and less-toxic therapies.
Therapeutic advances in musculoskeletal disease 12/2011; 3(6):315-24. DOI:10.1177/1759720X11415306
[Show abstract][Hide abstract] ABSTRACT: There is a paucity of literature on the patterns and predictors of mortality in idiopathic inflammatory myopathies (IIM).
To determine the patterns and predictors of mortality in a South Australian cohort of patients with biopsy-proven IIM.
The living/deceased status (and for deceased patients the causes of death) of patients with histologically determined IIM was determined from the Births, Deaths and Marriages Registry. Standardised mortality ratios (SMR) were generated compared with the age/gender matched South Australian population. The effect of presence/absence of the components of the Bohan and Peter criteria on risk ratios (RR) for mortality was determined. The effect of comorbidities and autoantibodies on mortality was investigated.
The SMR for mortality in IIM was 1.75 and was significantly increased in all disease subgroups, being highest in patients with dermatomyositis (2.40). Dominant causes of death were cardiovascular disease (31%), infections (22%) and malignancy (11%). Risk factors for death were age at time of biopsy (hazard ratio 1.05), ischaemic heart disease (RR 2.97, P < 0.0001), proximal weakness at diagnosis (RR 1.8, P= 0.03), definite diagnosis of IIM per the Bohan and Peter criteria (RR 2.14, P < 0.0001), and the absence of autoantibodies (RR 1.9, P < 0.001).
Patients with IIM are at 75% increased risk for mortality, and cardiovascular diseases account for the commonest causes of death. This study suggests a thorough cardiovascular evaluation of these patients is indicated, and raises the possibility that targeted interventions such as the use of aspirin or statins may improve outcomes in IIM.
Internal Medicine Journal 12/2010; 42(2):191-8. DOI:10.1111/j.1445-5994.2010.02406.x · 1.64 Impact Factor
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